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Synthetic retinoid CD437 induces mitochondria-mediated apoptosis in hepatocellular carcinoma cells |
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| Authors: | Gonda Kazue Tsuchiya Hiroyuki Sakabe Tomohiko Akechi Yuji Ikeda Remina Nishio Ren Terabayashi Kei Ishii Kyoko Matsumi Yoshiaki Ashla An Afida Okamoto Hideharu Takubo Kazuko Matsuoka Saori Watanabe Yumi Hoshikawa Yoshiko Kurimasa Akihiro Shiota Goshi |
| Affiliation: | a Division of Molecular and Genetic Medicine, Department of Genetic Medicine and regenerative Therapeutics, Graduate School of Medicine, Tottori University, Nishi-cho 86, Yonago 683-8504, Japan b Division of Oral and Maxillofacial Biopathological Surgery, Department of Medicine of Sensory and Motor Organs, Tottori University, Japan c Shimane Prefectural Central Hospital, Himebara 4-1, Izumo, Shimane, Japan d Watanabe Children and Ladies Clinic, Takeshi-cho 836-3, Izumo, Shimane, Japan |
| Abstract: | Retinoids play an important role in the regulation of cell growth and death. Synthetic retinoid CD437 reportedly induces apoptosis in various cancer cell lines. However, the mechanism of inducing apoptosis in hepatocellular carcinoma (HCC) cells by this agent remains to be clarified. In this study, we investigated the signaling pathway by which CD437 induces apoptosis in HCC cell lines. Apoptosis of six human HCC cell lines was induced by treatment with CD437. Caspase-3 and -9 were activated by CD437, suggesting that the apoptosis is mediated by mitochondrial pathways. Consistent with these findings, the treatment with CD437 upregulated Bax protein, downregulated Bcl-2 protein and released cytochrome c into the cytoplasm. Moreover, rhodamine123 staining revealed mitochondrial depolarization in the cells treated with CD437. These data of the present study suggest that CD437 induces apoptosis in HCC cells via mitochondrial pathways. |
| Keywords: | Synthetic retinoid CD437 Apoptosis Hepatocellular carcinoma Mitochondria |
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